An exploratory, randomized, double-blind, placebo controlled study to assess the efficacy of multiple doses of omalizumab in cystic fibrosis complicated with allergic bronchopulmonary aspergillosis

1. Males/females age >= 12 years
2. Cystic Fibrosis diagnosed by either gene profiling and/or sweat test
3. ABPA previously diagnosed according to the Cystic Fibrosis Foundation Consensus
Conference recommendations - minimal diagnostic criteria for diagnosis of ABPA in
cystic fibrosis (Stevens et al, 2003) defined as:
i) Acute or sub-acute clinical deterioration (cough, wheeze, exercise intolerance,
exercise-induced asthma, change in pulmonary function, or increased sputum
production) not attributable to another etiology.
ii) Total serum IgE concentration of >500 IU/mL (1200 ng/mL).
iii) Immediate cutaneous reactivity to Aspergillus (prick skin test wheal >3mm in
diameter with surrounding erythema, while the patient is not being treated with
systemic antihistamines) or in vitro demonstration of IgE antibody to A.fumigatus.
iv) One of the following:
a)precipitans to A.fumigatus or in vitro demonstration of IgG antibody to A.fumigatus
or
b)new or recent abnormalities on chest radiography (infiltrates or mucus plugging)
or chest CT (bronchiectasis) that has not cleared with antibiotics and standard
physiotherapy.
3. Total serum IgE level of > 500 IU/ml (will be measured locally at Screening Visit).
Screening IgE levels will determine the dose throughout the study.
4. Patients who are being treated for ABPA by any oral corticosteroid (for at least 8 weeks
prior to the first dose of study treatment - with an OCS entry dose of minimum
5mg/maximum 40mg per day in prednisolone equivalence). Patients must have a history
of at least one unsuccessful attempt to taper steroids defined as in the clinician*s
judgment, an ABPA exacerbation during taper (chronic ABPA group)
OR
Patients who present with an acute episode of ABPA, either as a first presentation or as a
recurrence, and who were taking a maximum dose of prednisolone of 20mg/day (or
equivalent) prior to the ABPA flare (acute ABPA group)
5. Patients must have an FEV1, as measured at the Baseline Visit, of no lower than 90% of
their previous best FEV1 as measured at Screening Visit
6. FEV1 >40% of predicted in patients aged < 16 years old, and FEV1 of >30% of predicted
is acceptable in patients aged >= 16 years old as measured after 12 hour washout of LABA
\ 6 hours of SABA
7. Female subjects of childbearing potential must be advised that systemic corticosteroids
pose a known risk to mother and fetus. Xolair is FDA pregnancy category B. This
medication is not expected to be harmful to an unborn. However, patients are advised to
use adequate methods of contraception, (e.g. hormonal contraceptive plus condom, intrauterine
device plus condom, spermicidal gel plus condom, diaphragm plus condom, etc.),
from the time of screening and for the duration of the study, through study completion.
Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods)
and withdrawal are not adequate methods of contraception
8. Female subjects who report surgical sterilization must have had the procedure at least six
(6) months prior to initial dosing. Surgical sterilization procedures should be supported
with clinical documentation made available to the sponsor and noted in the Relevant
Medical History / Current Medical Conditions section of the CRF
9. Postmenopausal females must have had no regular menstrual bleeding for at least one (1)
year prior to initial dosing. Menopause will be confirmed by a plasma FSH level of >40
IU/L at screening.
10. Prior to administration of any study procedures, eligible patients (and parents for
patients below age 16) must provide written informed consent
11. Subjects must be able to communicate well with the investigator; understand and comply
with the requirements of the study; and understand and sign the written informed consent
(parental consent and assent for minors, if applicable).

1. History of cancer in the past 10 years (except surgically-cured basal cell or squamous cell skin cancer).
2. Any previous history of anaphylaxis.
3. Any other medical condition that in the opinion of the investigator may cause the patient
to be unsuitable for completion of the study or place the patient at potential risk from
being in the study.
4. Pregnant women.
5. Prior Xolair exposure.
6. Lung or other transplant.
7. Participation in any clinical trial within four (4) weeks prior to initial dosing or longer if
required by local regulations, and for any other limitation of participation based on local
regulations.
8. Hemoglobin levels below 10.0 g/dl at screening.
9. History of immunodeficiency diseases.
10. Significant illness other than CF/ABPA within two (2) weeks prior to initial dosing.
11. A past medical history of clinically significant ECG abnormalities.
12. Patients who are known to be positive for chronic atypical Mycobacteria and Burkholderia
cepacia including subspecies.